He played college football for the Marshall Thundering Herd, winning the Sammy Baugh Trophy as a senior, and was selected by the New York Jets in the first round of the 2000 NFL draft.

In 1995, he went to a training camp at Marshall University, his parents' alma mater, where he was noticed by head football coach Jim Donnan and offered a scholarship.

The following year, Pennington was redshirted in favor of Eric Kresser, a transfer from the Florida Gators, who guided the Herd's return to the I-AA Championship game (a victory) in 1996.

[3] In addition to his success on the football field, Pennington excelled academically, graduating with a degree in journalism, a 3.83 grade point average and becoming a finalist for the Rhodes Scholarship.

He wrote frequently for Marshall's newspaper The Parthenon and was a broadcaster for the school's radio station WMUL, although he used a pseudonym on air so as not to be distracting.

Pennington helped reverse the Jets' fortunes by leading the 1–4 team to an eventual 9–7 record and an AFC East division championship.

In the Wild Card game, Pennington threw for a 142 QB rating, leading the Jets over Peyton Manning and the number four passing offense of the Indianapolis Colts.

Despite a scuffle with the New York media and losses to the New England Patriots and the St. Louis Rams, the Jets earned a wild card berth with a 10–6 record.

Pennington then led the Jets to a first-round, 20–17 overtime win against the AFC West Champion San Diego Chargers, as he went 23–33, for 279 yards and two touchdowns.

However, Pennington and the Jets would see their season end with kicker Doug Brien missing two potential game-winning field goals.

During a news conference on December 20, 2004, Pennington scolded the assembled media, telling them it was 'not (their) right' but a 'privilege' of theirs to cover the Jets, 'to be around a bunch of professional athletes every day and do your job'.

A dismal performance against the Kansas City Chiefs in September and a lackluster one against the Miami Dolphins the following week led to speculation that the shoulder had yet to fully heal, but both Pennington and Jets coach Herman Edwards denied this, citing a lack of pre-season practice and Pennington's less-than-full grasp of new offensive coordinator Mike Heimerdinger's plays.

On September 25, 2005, against the Jacksonville Jaguars, Pennington once again suffered an injury, although he re-entered the game later and almost led the Jets to victory despite not throwing well.

In the midst of the eventually-resolved labor talks of February–March 2006, Pennington restructured his contract with the New York Jets to ensure he remained with the team for at least the 2006 season.

Pennington was reported to have taken a significant cut in pay, with the amounts lost recoverable by way of achievable incentives; however, the Jets organization did not comment on contractual issues.

Using a short passing game and taking advantage of the "yards after catch" ability of wide receivers Laveranues Coles, Jerricho Cotchery, and running back Leon Washington, Pennington led the Jets to a 10–6 record and a playoff berth as a wild card team, a significant improvement over their 4–12 mark in 2005.

After leading the Jets to a dismal 1–7 start, coach Eric Mangini decided to bench Pennington for second-year quarterback Kellen Clemens.

Clemens suffered a rib injury during a Week 15 matchup against the Patriots, resulting in Pennington's return to game action.

In 2008, upon entering training camp, Eric Mangini announced a competition for the starting quarterback position between Pennington and Clemens.

However, on August 7, 2008, the Jets acquired veteran and former Green Bay Packers quarterback Brett Favre, leading to Pennington's release later that day.

[16] His 67.4 completion percentage led the NFL and broke Miami's single-season record of 64.2 set by Dan Marino in 1984.

For his role in the Dolphins' ten-win turnaround, Pennington received notable MVP consideration from several major media outlets.

[17][18] He received four votes, and finished tied for second with running back Michael Turner for the 2008 AP NFL MVP.

[21] He was officially placed on injured reserve and the Dolphins acquired Tyler Thigpen from the Chiefs for an undisclosed 2010 draft pick.

[35] Chad and Robin Pennington created the 1st and 10 Foundation in 2003 with the mission to build stronger communities by funding programs and institutions that seek to improve quality of life throughout West Virginia, Tennessee, and the New York metropolitan area.

[37] In 2018, Pennington was hired to be the head coach at Lexington, Kentucky's Sayre School, which was restarting a football program after a 40-year absence.